Tumor necrosis factor mediates zymosan-induced increase in glucose flux and insulin resistance

F. Petit, G. J. Bagby, C. H. Lang

Research output: Contribution to journalArticle

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Abstract

Intraperitoneal injection of sterile zymosan produces an inflammatory response ultimately resulting in multiple-organ failure. The purpose of the present study was to characterize the hormonal and metabolic alterations produced as a result of this nonbacterial nonendotoxic inflammatory agent and to determine whether these changes were mediated by enhanced production of tumor necrosis factor (TNF). Rats were injected intraperitoneally with either zymosan or saline and studied 18 h later. Under basal conditions, zymosan- injected rats were euglycemic but showed a 43% increase in hepatic glucose production and peripheral glucose uptake. The enhanced glucose flux in zymosan-treated rats was associated with elevations in plasma insulin (45%), glucagon (5-fold), corticosterone (2-fold), epinephrine (34%), and norepinephrine (115%). In vivo studies using 2-deoxyglucose (2-DG) demonstrated that the zymosan-induced increase in whole body glucose disposal resulted from an enhanced uptake by skeletal muscle (68%), diaphragm (3.7- fold), liver (144%), spleen (52%), and fat (133%). Under euglycemic hyperinsulinemic conditions, zymosan-treated rats exhibited both hepatic and peripheral insulin resistance, with the latter resulting from a decreased insulin-mediated glucose uptake by skeletal muscle, heart and diaphragm. Arterial TNF levels were increased by i h and remained elevated throughout the experimental protocol. Pretreatment of rats with a neutralizing anti-TNF antibody before zymosan prevented the elevation in basal glucose flux and attenuated the insulin resistance. We conclude that the inflammatory state induced by zymosan enhances basal glucose turnover and impairs insulin action and that these changes appear to be largely due to the enhanced endogenous production of TNF.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume268
Issue number2 31-2
StatePublished - Jan 1 1995

Fingerprint

Zymosan
Insulin Resistance
Tumor Necrosis Factor-alpha
Glucose
Insulin
Diaphragm
Liver
Skeletal Muscle
Multiple Organ Failure
Deoxyglucose
Corticosterone
Intraperitoneal Injections
Glucagon
Vascular Resistance
Epinephrine
Norepinephrine
Spleen
Fats
Antibodies

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

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abstract = "Intraperitoneal injection of sterile zymosan produces an inflammatory response ultimately resulting in multiple-organ failure. The purpose of the present study was to characterize the hormonal and metabolic alterations produced as a result of this nonbacterial nonendotoxic inflammatory agent and to determine whether these changes were mediated by enhanced production of tumor necrosis factor (TNF). Rats were injected intraperitoneally with either zymosan or saline and studied 18 h later. Under basal conditions, zymosan- injected rats were euglycemic but showed a 43{\%} increase in hepatic glucose production and peripheral glucose uptake. The enhanced glucose flux in zymosan-treated rats was associated with elevations in plasma insulin (45{\%}), glucagon (5-fold), corticosterone (2-fold), epinephrine (34{\%}), and norepinephrine (115{\%}). In vivo studies using 2-deoxyglucose (2-DG) demonstrated that the zymosan-induced increase in whole body glucose disposal resulted from an enhanced uptake by skeletal muscle (68{\%}), diaphragm (3.7- fold), liver (144{\%}), spleen (52{\%}), and fat (133{\%}). Under euglycemic hyperinsulinemic conditions, zymosan-treated rats exhibited both hepatic and peripheral insulin resistance, with the latter resulting from a decreased insulin-mediated glucose uptake by skeletal muscle, heart and diaphragm. Arterial TNF levels were increased by i h and remained elevated throughout the experimental protocol. Pretreatment of rats with a neutralizing anti-TNF antibody before zymosan prevented the elevation in basal glucose flux and attenuated the insulin resistance. We conclude that the inflammatory state induced by zymosan enhances basal glucose turnover and impairs insulin action and that these changes appear to be largely due to the enhanced endogenous production of TNF.",
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Tumor necrosis factor mediates zymosan-induced increase in glucose flux and insulin resistance. / Petit, F.; Bagby, G. J.; Lang, C. H.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 268, No. 2 31-2, 01.01.1995.

Research output: Contribution to journalArticle

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